NM_002471.4(MYH6):c.3809G>A (p.Arg1270His) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 26, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000658367.4

Allele description [Variation Report for NM_002471.4(MYH6):c.3809G>A (p.Arg1270His)]

NM_002471.4(MYH6):c.3809G>A (p.Arg1270His)

Gene:

MYH6:myosin heavy chain 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_002471.4(MYH6):c.3809G>A (p.Arg1270His)

HGVS:

NC_000014.9:g.23389643C>T
NG_023444.1:g.23635G>A
NM_002471.4:c.3809G>AMANE SELECT
NP_002462.2:p.Arg1270His
NP_002462.2:p.Arg1270His
LRG_389t1:c.3809G>A
LRG_389:g.23635G>A
LRG_389p1:p.Arg1270His
NC_000014.8:g.23858852C>T
NM_002471.3:c.3809G>A

Protein change:

R1270H

Links:

dbSNP: rs767603407

NCBI 1000 Genomes Browser:

rs767603407

Molecular consequence:

NM_002471.4:c.3809G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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RecName: Full=Hemoglobin subunit beta; AltName: Full=Beta-globin; AltName: Full=...
RecName: Full=Hemoglobin subunit beta; AltName: Full=Beta-globin; AltName: Full=Hemoglobin beta chain
gi|122702|sp|P04245.1|HBB_TRAST

Protein
BioProject Links for Protein (Select 4504481) (2)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000780139	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (May 25, 2018)	germline	clinical testing	Citation Link,
SCV003809564	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 26, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000780139

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(May 25, 2018)

germline

clinical testing

Citation Link,

SCV003809564

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 26, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000780139.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The R1270H variant of uncertain significance in the MYH6 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, the R1270H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003809564.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 16, 2024

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